Optimality of random allocation design for the control of accidental bias in sequential experiments

In comparing two treatments, suppose the suitable subjects arrive sequentially and must be treated at once. Known or unknown to the experimenter there may be nuisance factors systematically affecting the subjects. Accidental bias is a measure of the influence of these factors in the analysis of data. We show in this paper that the random allocation design minimizes the accidental bias among all designs that allocate n, out of 2n, subjects to each treatment and do not prefer either treatment in the assignment. When the final imbalance is allowed to be nonzero, optimal and efficient designs are given. In particular the random allocation design is shown to be very efficient in this broader setup.     

A new 'biased coin design' for the sequential allocation of two treatments

Summary.  Efron's biased coin design is a well-known randomization technique that helps to neutralize selection bias in sequential clinical trials for comparing treatments, while keeping the experiment fairly balanced. Extensions of the biased coin design have been proposed by several researchers who have focused mainly on the large sample properties of their designs. We modify Efron's procedure by introducing an adjustable biased coin design, which is more flexible than his. We compare it with other existing coin designs; in terms of balance and lack of predictability, its performance for small samples appears in many cases to be an improvement with respect to the other sequential randomized allocation procedures.     

A formula for a missing plot in a general incomplete block design,when recovery of interblock information is used

In this paper, Yate's missing plot technique is used to derive the formula for substitution in a missing plot in a general incomplete block design, where blocks are assumed to be independent normal. The use of penalized normal equations, using BLUPS, makes this task simpler.     

A study of several useful tests for ordered alternatives in the randomized block design

This study investigates the small sample powers of several tests designed against ordered location alternatives in randomized block experiments. The results are intended to aid the researcher in the selection process. Toward this end the small sample powers of three classes of rank tests — tests based on ‘within-blocks’ rankings (W-tests), ‘among-b locks’ rankings (A-tests), and ‘ranking after alignment’ within blocks (RAA-tests)— are compared and contrasted with the asymptotic properties given by Pirie (1974) as well as with the empirical powers of competing parametric procedures.     

Exact confidence limits for the probability of response in two-stage designs

In addition to point estimate for the probability of response in a two-stage design (e.g. Simon's two-stage design for binary endpoints), confidence limits should be computed and reported. The current method of inverting the p-value function to compute the confidence interval does not guarantee coverage probability in a two-stage setting. The existing exact approach to calculate one-sided limits is based on the overall number of responses to order the sample space. This approach could be conservative because many sample points have the same limits. We propose a new exact one-sided interval based on p-value for the sample space ordering. Exact intervals are computed by using binomial distributions directly, instead of a normal approximation. Both exact intervals preserve the nominal confidence level. The proposed exact interval based on the p-value generally performs better than the other exact interval with regard to expected length and simple average length of confidence intervals.     

A monte carlo study of the f test and three tests based on ranks of treatment effects in randomized block designs

The F test is compared with three procedures based on ranks for testing treatment effects in the randomized complete block, fixed effects, model with one observation per cell.     

A study of the properties of Gaussian mixture model for stable isotope standard quantification in MALDI-TOF MS

The quantification of peptides in Matrix assisted laser desorption/ionization time-of-flight mass spectrum analysis coupled with stable isotope standards has been used to quantify native peptides under many experimental conditions. This approach has difficulties quantifying samples containing peptides with ion currents in overlapping (convolved) spectra. In a previous article we proposed a reparametrized Gaussian mixture model based on the known characteristics of the peptides that could also accommodate overlapping spectra. We demonstrated the application of our model in a series of single and overlapping peptides quantification experiments. Here, we focus solely on studying the properties of our approach and examine the characteristics of the GMM approach in convolved peptides using simulated spectra and provide a method for simulating these spectra.     

Controlling for confounding via propensity score methods can result in biased estimation of the conditional AUC: A simulation study

In the medical literature, there has been an increased interest in evaluating association between exposure and outcomes using nonrandomized observational studies. However, because assignments to exposure are not random in observational studies, comparisons of outcomes between exposed and nonexposed subjects must account for the effect of confounders. Propensity score methods have been widely used to control for confounding, when estimating exposure effect. Previous studies have shown that conditioning on the propensity score results in biased estimation of conditional odds ratio and hazard ratio. However, research is lacking on the performance of propensity score methods for covariate adjustment when estimating the area under the ROC curve (AUC). In this paper, AUC is proposed as measure of effect when outcomes are continuous. The AUC is interpreted as the probability that a randomly selected nonexposed subject has a better response than a randomly selected exposed subject. A series of simulations has been conducted to examine the performance of propensity score methods when association between exposure and outcomes is quantified by AUC; this includes determining the optimal choice of variables for the propensity score models. Additionally, the propensity score approach is compared with that of the conventional regression approach to adjust for covariates with the AUC. The choice of the best estimator depends on bias, relative bias, and root mean squared error. Finally, an example looking at the relationship of depression/anxiety and pain intensity in people with sickle cell disease is used to illustrate the estimation of the adjusted AUC using the proposed approaches.